反应详情

温度

85 °C

A 20-mL vial was charged with (S)-2-methyl-4-(2-thiophenylsulfonyl)piperazine hydrochloride (0.75 g, 2.6 mmol, Example 27), (2-chloro-5-pyrimidinyl)-1,1,1,3,3,3-hexafluoro-2-propanol (0.92 g, 3.3 mmol, Intermediate D), 15 mL of dioxane, and Hünig's base (1.2 mL, 6.6 mmol). The mixture was heated at 85° C. for 12 h and then concentrated and purified via column chromatography on silica gel (0 to 50% EtOAc in hexanes) delivered 1,1,1,3,3,3-hexafluoro-2-(2-((2S)-2-methyl-4-(2-thiophenylsulfonyl)-1-piperazinyl)-5-pyrimidinyl)-2-propanol (0.360 g). 1H NMR (400 MHz, CD3OD) δ=8.58 (s, 2H), 7.87 (d, J=5.1 Hz, 1H), 7.66-7.63 (m, 1H), 7.28-7.23 (m, 1H), 5.14 (br. s., 1H), 4.76 (d, J=13.9 Hz, 1H), 3.83 (d, J=11.3 Hz, 1H), 3.67 (d, J=11.5 Hz, 1H), 3.40 (s, 1H), 2.69-2.58 (m, 1H), 2.47 (dt, J=3.6, 12.0 Hz, 1H), 1.36 (d, J=6.7 Hz, 3H). m/z (ESI, +ve ion) 491.0 (M+H)+. GK-GKRP IC50 (Binding)=0.362 μM; GK-GKRP EC50 (LC MS/MS-2)=0.470 μM.

1. concentrationconcentrated
2. custompurified via column chromatography on silica gel (0 to 50% EtOAc in hexanes)